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The Fertility Show

Issue 644 (13 February 2012)

 

Welcome to BioNews by email, published by the Progress Educational Trust, providing you with news, comment and reviews on genetics, assisted conception, embryo/stem cell research and related areas.

Visit the BioNews website at www.bionews.org.uk where you can subscribe for free to receive BioNews by email in one of three formats, and search the archive of more than 6,000 articles.

 

 

CONTENTS

Comment

News Digest

Reviews


 



Beyond the treatment of infertility

13 February 2012

By Professor Mary Herbert

Professor of Reproductive Biology at Newcastle University and Honorary Consultant Embryologist at Newcastle Fertility Centre

Appeared in BioNews 644
The advent of PGD extended the scope of IVF beyond the treatment of infertility. PGD involves the removal of one or two cells from the early embryo to test for a specific genetic defect. It is predominantly used to prevent transmission of genetic defects arising from mutations in nuclear DNA, which encodes the characteristics we inherit from our parents. However, PGD can also be used to reduce the risk of transmitting mutations in mitochondrial DNA (mtDNA), which cause a range of debilitating and life-threatening diseases.

Mitochondrial DNA is contained in mitochondria (the cell's batteries), which are dispersed throughout the cell. Unlike nuclear DNA, which we inherit from both parents, mtDNA is inherited exclusively from our mothers. Mutations in mtDNA can either be present in all mitochondria or in only a proportion of mitochondria. In the latter case, known as heteroplasmy, the severity of disease is proportional to the ratio of mutated to non-mutated mtDNA.

Because of the manner in which mitochondria segregate to different cell types during embryonic development, a woman who is heteroplasmic for a given mutation, and who herself has a low mutation load, can produce eggs with varying levels of mutation. Consequently, some embryos may contain sufficiently high levels to cause serious disease in the child. By sampling a cell from the embryo it is possible to select those with the lowest mutation load, thereby reducing the risk of disease. However, PGD is not useful for homoplasmic women, whose entire complement of mtDNA carries the mutation. Likewise, the embryos of a heteroplasmic woman with a high mutation load are likely to also contain a high proportion of mutated mtDNA.

An alternative approach, currently being developed, is to rid the egg of affected mitochondria. As the egg contains hundreds of thousands of mitochondria, it is not practical to transplant the mitochondria themselves. However, it is possible to transplant the nuclear DNA into another egg. In theory, this approach could be used to create a reconstituted egg containing nuclear DNA from the affected woman and mtDNA from an unaffected donor. This would enable women with mutated mtDNA to have a genetically related child without transmitting mtDNA disease.

Two approaches to nuclear DNA transplantation are currently being explored. The first, which has been extensively tested in mice, is to transplant the nuclear DNA after the egg has been fertilised. At this stage the nuclear DNA from the egg and sperm is contained in two large structures, called the pronuclei, which are visible under the light microscope and can be transferred between fertilised eggs. The other approach is to transplant the nuclear DNA before fertilisation. At this stage the egg's nuclear DNA, poised to halve its content following sperm entry, is positioned within a structure known as the second meiotic spindle. Using specialised optics it is possible to visualise the spindle and to transplant it, together with the nuclear DNA, to another oocyte (egg). Pronuclear transfer has been found to be technically feasible in human eggs (1) and live births have been reported following spindle transfer in monkey oocytes (2). Either technique could, in principle, be used to dramatically reduce the risk of transmission of mtDNA disease.

Because the mitochondria are scattered throughout the egg, it is likely that a small proportion of mutated mtDNA will be transferred with the nuclear DNA. Thus, it is possible that the reconstituted egg will contain a small amount of mutated mtDNA. Studies in monkeys and humans indicate that this accounts for less than two percent of total mtDNA, whereas the threshold for disease is in the region of 60 percent mutation. Thus, on the basis of our current understanding, it is highly unlikely that a child born following pronuclear or spindle transfer will develop mtDNA disease. Nonetheless, ongoing research seeks to further reduce the level of mtDNA carryover.

The next big step is to determine which technique (pronuclear or spindle transfer) is likely to be the most efficient in terms of producing viable embryos. It will also be very important to determine whether embryos derived from reconstituted eggs differ from embryos produced by conventional IVF/ICSI procedures. While it was possible to perform proof of principle studies using abnormally fertilised human eggs, development of these embryos is impaired, making it impossible to perform meaningful analysis of safety and efficacy. It is therefore necessary to use eggs donated and fertilised specifically for the purpose of this research. Thus, the research, and indeed any future clinical application, will require a supply of donated eggs.

It is hoped that these studies will provide the evidence required for the regulators to make a decision on the suitability of nuclear DNA transplantation for clinical application. From a clinical embryology perspective, this is an enormously exciting development, which has the potential to further extend the scope of IVF-based technologies in preventing otherwise incurable diseases.

 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

17 September 2012 - by Dr Sophie Pryor 
The UK's Human Fertilisation and Embryology Authority (HFEA) has launched a public consultation on the social and ethical impact of new methods that could prevent the transmission of some incurable mitochondrial diseases.... [Read More]
09 July 2012 - by Sarah Guy 
It is now scientifically feasible to use preimplantation genetic diagnosis (PGD) during IVF to screen embryos for genes associated with high cancer risk, scientists say... [Read More]
25 June 2012 - by Dr Virginia Bolton 
Predictably, the publication of the Nuffield Council on Bioethics' report supporting further research into a technique to prevent inheritance of mitochondrial disease prompted a flurry of publicity. Equally predictably, nearly every newspaper - whether broadsheet or tabloid - went for the sensationalist angle and used the 'three-parent IVF' tag in their headline... [Read More]

23 January 2012 - by Maria Botcharova 
An experimental genetic technique to prevent serious diseases from passing between mother and child is to receive £5.8 million funding. The Wellcome Trust is contributing £4.4 million to the new Centre for Mitochondrial Research at Newcastle University... [Read More]
06 June 2011 - by Marianne Neary 
Women at risk of passing on mitochondrial disease to their children could use PGD to give birth to an unaffected child. The scientists at Maastricht University Medical Centre in the Netherlands claim their work has the potential to prevent the transmission of mitochondrial diseases... [Read More]
03 May 2011 - by Professor Alison Murdoch 
Medicine has faced many controversial milestones, none more so than those involving reproduction. The UK Government must now decide whether we can use IVF technology to reduce the risk of transmission of mitochondrial DNA abnormalities. Will they accept it or reject it?... [Read More]
03 May 2011 - by MacKenna Roberts 
Further research is needed into the safety and effectiveness of techniques to prevent children being born with mitochondrial disease, a Human Fertilisation and Embryology Authority (HFEA) report has concluded... [Read More]
19 April 2010 - by Dr Kristina Mills and Dr Marita Pohlschmidt 
Research at Newcastle University funded by the Muscular Dystrophy Campaign has shown that it might be possible to prevent mitochondrial diseases being passed from mother to child... [Read More]



Why we should back a law change to allow mitochondrial transfer into the clinic

13 February 2012

By Dr Kristina Elvidge

Research Communications Officer, Muscular Dystrophy Campaign, UK

Appeared in BioNews 644
Mitochondrial diseases are soon to be brought to the attention of the general public, as the Government seeks to gauge the attitude of the nation towards a ground-breaking IVF treatment that could prevent these conditions being passed from mother to child (1).

It is estimated that 3,500 people in the UK have mitochondrial myopathies; a group of incurable mitochondrial diseases which, in the most severe cases, can cause debilitating and life-threatening muscle weakness. Life is made even more difficult for affected families as it is almost impossible to provide them with accurate genetic counselling and family planning advice.

Mitochondria are found in every cell in our body, except for red blood cells; they are the 'batteries' that provide energy to the cell. Mitochondria have their own small piece of DNA that is inherited only through the maternal line, so unlike most mutations in the chromosomes, mitochondrial DNA mutations are likely to be passed onto all offspring. Generally cells have a mixture of normal and abnormal mitochondria and the proportion of each determines the disease severity. The proportions are unstable and differ from egg to egg so it is very difficult to predict how severely a child will be affected. This makes the decision to have children a heart-wrenching gamble for families affected by mitochondrial disease.

In order to tackle these debilitating diseases, the Muscular Dystrophy Campaign has supported Professor Doug Turnbull's world-leading mitochondrial research at the University of Newcastle for the past 20 years, providing more than £1.2 million worth of funding in that time. This has culminated in the development of a technique with the potential to prevent mitochondrial diseases being passed from mother to child.

This technique involves replacing the faulty mitochondria with healthy mitochondria from a donated egg. This is done as part of the IVF process, either before an egg is fertilised (using a technique called maternal spindle transfer) or after fertilisation (pronuclear transfer). These techniques have proven successful (2, 3) at replacing the mitochondria in the laboratory.

If these techniques were to come into clinical practice they would give families affected by mitochondrial disease the opportunity to have healthy children. However, there is still work to be done before this could happen because although research on these techniques is allowed in the laboratory, the law currently prohibits implantation of any resulting embryos into the mother.

The Secretary of State for Health asked the Human Fertilisation and Embryology Authority (HFEA), in February 2011, to carry out a scientific review to scope 'expert views on the effectiveness and safety of mitochondrial transfer'. This review (4) concluded that as these techniques are so new, further experiments would be required before advice could be given as to whether the first clinical trials should be allowed to go ahead.

Encouragingly, it was announced last month that a new Wellcome Trust Centre for Mitochondrial Research (5) will be set up in Newcastle which will allow this research to move forward. Professor Turnbull will be the Director of the new centre and researchers will carry out the tests they hope will satisfy the HFEA that these techniques are safe and effective.

Secondly, the Government asked the HFEA and Sciencewise-ERC to seek the views of the general public on the possible use of these techniques in the clinic (6).

Mitochondrial transfer would seem to be an immediately controversial topic. News of research in the field is frequently greeted with newspaper headlines talking of 'three-parent babies' while fears are voiced over designer babies being the next step.

And yet, were these techniques to be put to use in the clinic, less than 0.1 percent of the resulting baby's DNA would come from the donated egg, and these genes would only be involved in energy production via the mitochondria, and nothing else. The techniques have been developed specifically for mitochondrial diseases, are not applicable to any other types of genetic conditions and cannot be used to alter the genes in the chromosomes. Therefore an important aspect of the HFEA's public consultation will be to communicate the complicated science involved to the public and raise awareness of its implications.

The Muscular Dystrophy Campaign will be representing the patient voice during the public consultation to make sure the public are aware of the immense potential this technology has to help families at risk from mitochondrial myopathies. In the absence of a cure or treatment for these conditions, this technology currently has the amazing potential to transform lives by breaking the chain of inheritance within families.

 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

17 September 2012 - by Sarah Norcross 
Mitochondria don't normally get much press attention, they like to keep a low profile generating energy in the cells and leave nuclear DNA to grab the headlines... [Read More]
17 September 2012 - by Dr Sophie Pryor 
The UK's Human Fertilisation and Embryology Authority (HFEA) has launched a public consultation on the social and ethical impact of new methods that could prevent the transmission of some incurable mitochondrial diseases.... [Read More]
25 June 2012 - by Dr Virginia Bolton 
Predictably, the publication of the Nuffield Council on Bioethics' report supporting further research into a technique to prevent inheritance of mitochondrial disease prompted a flurry of publicity. Equally predictably, nearly every newspaper - whether broadsheet or tabloid - went for the sensationalist angle and used the 'three-parent IVF' tag in their headline... [Read More]
18 June 2012 - by Dr Geoff Watts 
The Nuffield Council on Bioethics has published a new report: 'Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review'. Dr Geoff Watts, chair of the working party that wrote it, offers some personal reflections on a few of its key conclusions... [Read More]
12 June 2012 - by Antony Blackburn-Starza 
The Nuffield Council on Bioethics has published a review of the ethical issues raised by proposed IVF techniques, which aim to prevent the transmission of faulty mtDNA from mother to child. The report concludes the techniques are ethically permissible, provided further research establishes their safety.... [Read More]

23 January 2012 - by Maria Botcharova 
An experimental genetic technique to prevent serious diseases from passing between mother and child is to receive £5.8 million funding. The Wellcome Trust is contributing £4.4 million to the new Centre for Mitochondrial Research at Newcastle University... [Read More]
06 June 2011 - by Marianne Neary 
Women at risk of passing on mitochondrial disease to their children could use PGD to give birth to an unaffected child. The scientists at Maastricht University Medical Centre in the Netherlands claim their work has the potential to prevent the transmission of mitochondrial diseases... [Read More]
03 May 2011 - by Professor Alison Murdoch 
Medicine has faced many controversial milestones, none more so than those involving reproduction. The UK Government must now decide whether we can use IVF technology to reduce the risk of transmission of mitochondrial DNA abnormalities. Will they accept it or reject it?... [Read More]
14 March 2011 - by MacKenna Roberts 
Health Secretary, Andrew Lansley has asked the Human Fertilisation and Embryology Authority (HFEA) to convene an expert group 'to assess the effectiveness and safety' of a fertility treatment that would enable children to be born without potentially devastating, incurable mitochondrial diseases.
19 April 2010 - by Dr Kristina Mills and Dr Marita Pohlschmidt 
Research at Newcastle University funded by the Muscular Dystrophy Campaign has shown that it might be possible to prevent mitochondrial diseases being passed from mother to child... [Read More]



Gene variant linked to common type of stroke

13 February 2012

By Luciana Strait

Appeared in BioNews 644

A genetic variant has been linked to an increased risk of a common type of stroke. Researchers identified an alteration in a gene called HDAC9 that is more common in people who have had an ischaemic stroke than in those who have not. The study also replicated variants previously associated with subtypes of ischaemic strokes.

Ischaemic strokes account for 80 percent of stroke cases, and occur when the blood flow to a part of the brain is blocked. This case-control study, published in Nature Genetics, found that the genetic variant was associated with an increased risk of a subtype of ischaemic stroke called a 'large vessel stroke'. This is where blood flow to the brain is blocked in one or more arteries.

Professor Peter Donnelly, director of the Wellcome Trust Centre for Human Genetics at the University of Oxford, who co-led the study, says: 'This is really fascinating, and if it holds up more generally, will move us closer to personalised medicine, where treatments and preventions can be tailored more precisely to individual patients'.

Overall, the international team of researchers examined genetic variants in around 10,000 people who had had an ischaemic stroke and around 40,000 healthy people. People can carry two copies of the variant, and the team estimates that each copy of the variant carried is associated with around a 42 percent increase in the odds of a large vessel stroke.

Although this study was thorough and well designed, it can only point to an association between a particular genetic variant and strokes. Further research is needed in order to establish whether the variants identified play a casual role in strokes, or if they lie close to other genetic variants that have this effect.

'This discovery identifies a completely new mechanism for causing stroke. The next step is to determine in more detail the relationship between HDAC9 and stroke and see whether we can develop new treatments that reduce the risk of stroke', says Professor Hugh Markus, from St George's, University of London, who co-led the study. 'Interestingly, there are already drugs available which inhibit the HDAC9 protein. However, it is important that we understand the mechanism involved before trialling the effects of these drugs on stroke'.

Strokes are one of the top two leading causes of death worldwide and a major cause of disability in developing countries.

Dr Peter Coleman, deputy director of research at The Stroke Association described the study as 'ground breaking'. 'Over a third of strokes are caused by a blockage in one of the large blood vessels supplying blood to the brain... Further study is needed, but this research could potentially lead to new methods of screening and prevention for large vessel stroke, and ultimately, new methods of treatment'.

 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

31 October 2011 - by Suzanne Elvidge 
Taking a daily aspirin has been recommended for people with a high risk of an inherited form of bowel cancer. Results published in The Lancet suggested the risk for those with Lynch syndrome could be cut by 63 percent... [Read More]
21 March 2011 - by Victoria Kay 
US scientists have identified a gene that may increase the risk of an early onset of stroke. They analysed the genomes of 14 Amish individuals affected by stroke and found a mutation in the SAMHD1 gene that was associated with the brain condition.... [Read More]
29 November 2010 - by Dr Rachael Panizzo 
A British man has become the first patient in the world to receive a pioneering stem cell therapy to repair brain damage caused by stroke.... [Read More]
10 May 2010 - by Marianne Neary 
Certain variations of mitochondrial DNA are protective against strokes, according to a recent study in The Lancet Neurology.... [Read More]
08 March 2010 - by Dr Rachael Panizzo 
A genetic risk score based on several genetic markers associated with cardiovascular disease (CVD) does not improve the prediction of CVD risk, research published in the Journal of the American Medical Association has suggested... [Read More]



Parkin gene researchers grow Parkinson's brain cells in lab

13 February 2012

By George Frodsham

Appeared in BioNews 644

Human brain cells with Parkinson's disease have been successfully grown in a Petri dish, allowing researchers to study them in unprecedented detail. American researchers used a technique in which human skin cells are transformed into induced pluripotent stem (iPS) cells, which can then be made to change into any cell type - in this case, neurons.

In the study, published in Nature Communications, skin cells were taken from two healthy donors and from two patients with a strain of Parkinson's disease that is caused by a mutation in the parkin gene. The neurons that resulted from the patients' skin cells possessed the same parkin mutation. The mutation is known to be the cause of the disease in about ten percent of Parkinson's patients; the cause in the remaining 90 percent of cases is unknown.

The work enabled the group to see how the parkin mutation causes Parkinson's. It will also allow researchers to investigate, up close, the effects of potential new treatments, and study other neurodegenerative diseases by observing neurons directly.

Study leader Dr Jian Feng, from the University at Buffalo in New York, said that this was the first time that brain cells had been generated from Parkinson's patients with parkin mutations: 'Before this, we didn't even think about being able to study the disease in human neurons. The brain is so fully integrated. It's impossible to obtain live human neurons to study'.

The parkin gene normally helps the brain control the levels of dopamine, a brain signalling chemical. When a mutation occurs an enzyme called monoamine oxidase (MAO), which is toxic to dopamine-producing cells, is produced uncontrollably, thereby killing neurons and causing Parkinson's disease.

'We found that when parkin is mutated, that regulation [of MAO] is gone, so MAO is [produced] at a much higher level', said Dr Feng. 'The nerve cells from our Parkinson's patients had much higher levels of MAO expression than those from our controls'.

Dr Feng said he hopes that the work will help further understanding of Parkinson's disease and develop new treatments: 'We suggest in our study that it might be possible to design a new class of drugs that would dial down the expression level of MAO'.

 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

02 December 2013 - by Matthew Thomas 
People with a particular genetic mutation may face greater risks of developing Parkinson's disease if exposed to certain pesticides, according to scientists... [Read More]
25 June 2012 - by Dr Daniel Grimes 
Human embryonic stem cells have, for the first time, been used to grow a crucial part of the eye, a paper in Cell Stem Cell reports. It is hoped that in the future transplantation of such tissue could help visually impaired people recover their sight... [Read More]
16 April 2012 - by Kimberley Bryon-Dodd 
A woman with Parkinson's disease is reportedly able to write again for the first time in 15 years after receiving pioneering gene therapy at Addenbrooke's Hospital, Cambridge. Mrs Shelia Roy took part in an early stage clinical trial of ProSavin - a treatment developed by biopharmaceutical company, Oxford BioMedica.... [Read More]
20 February 2012 - by Dr Caroline Hirst 
Skin cells from volunteers with Down's syndrome have been turned into brain cells in order to provide a new model for researchers to study Alzheimer's disease... [Read More]

14 November 2011 - by Luciana Strait 
Human embryonic stem cells have been used to treat a model of Parkinson's disease, rats and monkeys, pointing to a possible new way of treating the condition.... [Read More]
30 August 2011 - by Victoria Kay 
UK scientists have, for the first time, generated live nerve cells from a patient with a rapidly progressing form of Parkinson's disease... [Read More]
18 July 2011 - by Dr Lux Fatimathas 
US researchers have successfully converted human skin cells directly into brain nerve cells, skipping an intermediate stem cell stage. The new technique has the potential to aid research into neurodegenerative disorders of the brain, such as Parkinson's and Alzheimer's.... [Read More]
09 March 2009 - by Rose Palmer 
Scientists at the Whitehead institute for Biomedical Research in Massachusetts have successfully transformed human skins cells into stem cells that could be used to study and find treatments for Parkinson's disease. At the same time they removed the viruses usually used in the process, thereby minimising the... [Read More]



Gene therapy successfully treats inherited blindness

13 February 2012

By Maria Botcharova

Appeared in BioNews 644

Three women have reported a significant improvement in sight following gene therapy in both their eyes. Initially, they received the therapy in just one eye, but this latest study demonstrates the treatment was also successful in the other.

The first procedure, whose results were published in 2009, was carried out on 12 patients, and improved the sight of six to above the legal level for blindness.

'Our concern was that the first treatment might cause a vaccine-like immune response that could prime the individual's immune system to react against a repeat exposure', said lead author Dr Jean Bennett, of the University of Pennsylvania.

However, as reported in the journal Science Translational Medicine, the second treatment did not trigger this response, with improvements seen in as little as two weeks. The patients were able to see in dim light, read large print and recognise people's faces. Two of the three women were better able to find their way around obstacles.

The gene therapy targets a rare form of inherited blindness, called Leber's congenital amaurosis (LCA). The disorder severely affects sight from an early age, and often leads to complete blindness by the twenties or thirties.

Dr Bennett suggests that performing the procedure on children would be even more effective because the disorder will have progressed less.

LCA occurs because of a genetic mutation in cells found in the retina. The treatment involves injecting a patient with a healthy form of the gene, attached to a harmless virus. The virus spreads quickly among the unhealthy cells, acting like a Trojan horse, and leaves the correct gene in place of the mutation.

There were also some unexpected benefits from treatment of the second eye. A scan of brain regions that process vision showed that the previously treated eye improved further following the second procedure. Dr Bennett suggests that this may be because the two eyes were able to coordinate.

'That wasn't something we had been expecting, but it makes sense because the two eyes act in concert', she told Scientific American. Clara Eaglen, policy and campaigns manager at the Royal National Institute of Blind People (RNIB) says that the techniques should be studied more extensively.

'They can then be turned into effective treatments for a variety of more common degenerative eye conditions', she told BBC News.

 

SOURCES & REFERENCES
Science Translational Medicine | 08 February 2012
 
Pennsylvania Medicine press release | 08 February 2012
 
BBC | 08 February 2012
 
AFP | 09 February 2012
 
Scientific American | 08 February 2012
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

16 January 2014 - by Siobhan Chan 
Gene therapy for an eye condition called choroideremia is safe and has improved the vision of six patients, says a study in the Lancet... [Read More]
15 July 2013 - by Nicola Davis 
A clinical trial of a gene therapy to treat children with two types of severe genetic disease has shown early signs of success... [Read More]
18 February 2013 - by Maria Sheppard 
Twenty-four genes linked to short-sightedness have been identified by an international consortium of scientists... [Read More]
28 May 2012 - by Ana Pallesen 
Two patients with corneal blindness have become the first people in the UK to have stem cells transplanted into their eyes in order to restore their sight... [Read More]
12 March 2012 - by Dr Nadeem Shaikh 
A potential stem cell therapy for glaucoma – a degenerative eye condition that can lead to blindness – has yielded positive results in animal tests... [Read More]

06 February 2012 - by Ruth Retassie 
US company StemCells Inc have received Food and Drug Administration (FDA) authorisation to carry out clinical trials of their treatment for one of the leading causes of blindness in over 55-year-olds... [Read More]
31 January 2012 - by Dr Dusko Ilic and Dr Emma Stephenson 
Last week, Advanced Cell Technology (ACT) of Massachusetts, USA, made two important announcements regarding human embryonic stem (hES) cell-based therapies for the potential treatment of Stargardt's dystrophy and age-related macular degeneration, two devastating degenerative disease leading to blindness.... [Read More]
31 January 2012 - by Rosemary Paxman 
A clinical trial testing the safety of using human embryonic stem cell (hESC) in the treatment of progressive eye conditions has been carried out by researchers in the USA... [Read More]
31 January 2012 - by Dr Dusko Ilic 
In the last few months of 2011, a couple of stories on human embryonic stem cells hit the headlines. Both were bad news for stem cell researchers... [Read More]
31 October 2011 - by Victoria Kay 
A British man has become the first person to receive an advanced gene therapy treatment in a bid to save his sight. Jonathan Wyatt, aged 63, is the first of 12 patients to have the experimental procedure to try and halt the progression of his genetic eye disorder, choroideraemia. While he still has some sight, if left untreated, he would eventually become blind... [Read More]



Cord blood stem cell clinical trial for hearing loss begins

13 February 2012

By Dr Rebecca Hill

Appeared in BioNews 644

US researchers have received approval to test whether cord blood stem cells could be used to reverse hearing loss in children.

The phase I clinical trial, the first cord blood trial to be given the go-ahead by the US Food and Drug Administration (FDA), will determine the safety of the treatment. The team from the Children's Memorial Hermann Hospital in Houston will recruit ten children, aged six weeks to 18 months, who developed hearing loss after birth.

In 2008 a European team used human cord blood stem cells to reverse a kind of hearing loss - called sensorineural hearing loss - in mice. Dr Samer Fakhri, the principal investigator for the clinical trial, told the Winnipeg Free Press that these animal studies had been successful; after only two months the mice's 'inner ear organization and structure were basically restored'.

The majority of sensorineural hearing loss in humans is due to damaged hair cells in part of the inner ear called the cochlea. They are responsible for picking up and transferring signals to the brain to interpret.

It is not known how the stem cells repaired the damaged tissue in the mice - it could be that they regenerate these hair cells or that they initiate the body's own repair mechanisms.

'Currently, the only treatment options for sensorineural hearing loss are hearing aids or cochlear implants. We hope that this study will open avenues to additional treatment options for hearing loss in children', said Dr Fakhri.

The therapy will use stem cells taken from the patients' own cord blood, which has been banked at birth. At the start of the study the patients will have a brain scan, as well as blood, hearing and speech tests. Follow-up will be over the course of a year, with tests at one, six and twelve months post-treatment and a brain scan at six months.

It is stressed that the trial is primarily to assess the safety of injecting the stem cells into the children, and other researchers are treating the trial with care.

'We're a long way from looking at the possible therapeutic value of this in terms of restoring some sort of hearing', Dr Robert Harrison, a director of the Hearing Foundation of Canada, told the Winnipeg Free Press. 'It's a very theoretical concept, and in my opinion it's not going to happen soon'.

The study is being funded by the Cord Blood Registry and will take place at separate medical institutions in Texas and Georgia.

'If both of them can reproduce the same results then I would say it has some validity to it', Dr Stephen Epstein, an otolaryngologist in Maryland who is not involved in the study, told the AFP. 'This is certainly a welcome, acceptable experiment, but it should be looked at with caution and time will tell'.

 

SOURCES & REFERENCES
Cord Blood Registry | 12 January 2012
 
Study looks at whether stem cells in cord blood might repair hearing loss in kids
Winnipeg Free Press | 09 February 2012
 
AFP | 08 February 2012
 

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Cut IVF multiple births to 10 percent, says HFEA

13 February 2012

By Nishat Hyder

Appeared in BioNews 644

The rate of multiple births resulting from IVF treatment is to be no more than ten percent, announced the Human Fertility and Embryology Authority (HFEA), in the final stage of its policy to reduce IVF multiple birth rates in the UK.

In a letter to all fertility clinics, chief executive of the HFEA, Mr Alan Doran, explained as of 1 October 2012, no more than ten percent of a centre's annual births from IVF, ICSI and gamete intra-fallopian transfer (GIFT) treatments should be multiple. Births from intrauterine insemination (IUI) or DI are excluded.

The decision is part of the HFEA's multiple births policy and sets the final maximum - fourth year - birth rate target. Ordinarily the new target rate is introduced in April, but the decision gives clinics extra time to adopt strategies and implement changes as the target rate comes down. The letter explains meeting the current year three target of 15 percent has been 'challenging'.

Figures indicate that on average clinics were under the year one and year two targets (24 and 20 percent, respectively), and were on course to meet the current annual target. The HFEA says multiple births present the single biggest risk to the health of mothers and children born after IVF. It maintains the risk can be avoided by transferring only one embryo into women with greater chances of becoming pregnant.

In 2007 the HFEA adopted a policy to reduce the annual rate of multiple births following treatment at fertility clinics over a four year period to no more than ten percent. All clinics were required to have in place a strategy to minimise multiple births by January 2009, when the HFEA set the annual maximum multiple birth rate at 24 percent. It has set yearly targets since then.

A group was set up in 2007 to promote a national strategy encouraging elective single embryo transfer (eSET). The strategy says clinics should offer eSET to women they identify as most likely to become pregnant, and therefore most at risk of having a multiple birth.

In the letter, Doran noted that since the introduction of the HFEA's policy, 'the proportion of eSET has increased, the multiple pregnancy rate has decreased and the overall pregnancy rate has remained steady'.

'The pregnancy rates from elective single embryo transfer are similar to the pregnancy rates from double embryo transfer', he said.

Chairman of the Association of Clinical Embryologists, Ms Rachel Cutting, welcomed the new target but cautioned: 'The problem most clinicians have is when patients are paying for a cycle, it is hard to convince them to have just one embryo put back, because they automatically think two will give them a better chance'.

Cutting also pointed out that it would be easier for clinics to meet the 10 percent target if the NHS was to fund three cycles of IVF per couple - as recommended by the National Institute for Health and Clinical Excellence.

 

SOURCES & REFERENCES
BBC | 09 February 2012
 
HFEA | 09 February 2012
 
Telegraph | 09 February 2012
 

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25 November 2013 - by Ari Haque 
A report from the Office for National Statistics (ONS) shows that the number of multiple births among women over 45 has increased by 23 percent in the past year. The increase is thought to be in part due to more older women using IVF treatment to conceive... [Read More]
15 November 2013 - by Antony Blackburn-Starza 
The UK's High Court has ruled against the Human Fertilisation and Embryology Authority saying its actions towards two clinics over a licence condition to impose a maximum multiple birth rate were unlawful. The HFEA has now decided to withdraw the condition from all UK fertility clinics' licences... [Read More]
11 February 2013 - by Matthew Thomas 
Figures released by the UK's Human Fertilisation and Embryology Authority reveal the number of IVF cycles performed each year has continued to rise while the overall multiple pregnancy and birth rate has declined.... [Read More]
08 May 2012 - by Dr Rebecca Hill 
The increase in birth defects in babies born after assisted conception could be partly due to underlying fertility problems, according to an Australian study... [Read More]
20 February 2012 - by Victoria Kay 
The UK's fertility watchdog, the Human Fertilisation and Embryology Authority (HFEA), has amassed cash reserves of around £3.4 million from charges to the clinics it licenses, prompting calls for the money to be given back to those seeking IVF treatment.... [Read More]

31 January 2012 - by Ayesha Jadoon 
A new method of looking for chromosomal abnormalities in embryos can increase the chance of successful IVF implantation, a recent study in the journal Fertilisation In Vitro has shown.... [Read More]
16 January 2012 - by Dr Lux Fatimathas 
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09 January 2012 - by Victoria Kay 
There has been a rise in the number of British women choosing to give birth to fewer children following multiple pregnancy, leading to renewed calls for restrictions on the number of embryos implanted during IVF.... [Read More]
03 October 2011 - by Dr Rebecca Hill 
The National Institute for Health and Clinical Excellence (NICE) has issued new guidelines saying that women pregnant with twins or triplets should be monitored more closely, receiving specialist care from a team of healthcare professionals... [Read More]
16 May 2011 - by Chris Chatterton 
The UK's fertility regulator published a report last Thursday that it says indicates its success at reducing multiple births from fertility treatment by promoting elective single embryo transfer (eSET).... [Read More]



Gene passed from father to son added to list of heart disease risks

13 February 2012

By Dr Zara Mahmoud

Appeared in BioNews 644

A sixth of men have a genetic variant which could increase their risk of heart disease by up to 56 percent, according to a recent study.

The research, which looked at a subset of genes on the Y chromosome, which is only passed from father to son, might help to explain why men are at a higher risk for heart disease then women. The current lifetime risk for developing heart disease is one in two for men over 40, but only one in three for women in the same age group.

The team analysed 11 common genetic variants in the Y chromosomes of over 3,000 unrelated men, and used this to split them into subgroups. Men belonging to one of these groups, known as Haplotype I, were at a 56 percent higher risk for coronary artery disease (CAD) than men who did not inherit this haplotype.

This risk was independent of other factors, such as age, blood pressure, socioeconomic status, smoking or alcohol consumption.

'This gene variant is working through different mechanisms from the usual risk factors. It is difficult to say what the men affected can do about it because we don't yet understand its mechanism', said lead researcher Dr Maciej Tomaszewski, a senior clinical lecturer at the University of Leicester. 'The only advice we can give is to continue doing the good work in the department of lifestyle changes because that will reduce the risk of the known mechanisms'.

Further analysis revealed that some genes may be differentially expressed in those with haplotype I and other subgroups. While the exact role of these genes is unclear, some of them have been implicated in atherosclerosis.

The scientists conclude that it is too early to say that men should be tested for the gene, as more work is needed to decipher the complex interactions between the genes on the Y-chromosome, the immune system, and those already linked to increased risk of cardiovascular disease.

Dr Hélène Wilson of the British Heart Foundation, which part-funded the work, told the BBC: 'Lifestyle choices such as poor diet and smoking are major causes, but inherited factors carried in DNA are also part of the picture. The next step is to identify specifically which genes are responsible and how they might increase heart attack risk'.

 

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06 February 2012 - by Suzanne Elvidge 
The idea of whole genome sequencing is becoming ever more popular, but it could mean you end up with more information than you bargained for; from your resistance to certain drugs to your risk of developing a range of diseases. But would you want to know? The Wellcome Trust Sanger Institute ethics team has launched a survey to find out what people really do (and don't) want to know about their genomes... [Read More]
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Eating high quantities of fresh fruit and vegetables can counterbalance the effects of having a genetic predisposition to heart disease, an international study has found... [Read More]
19 September 2011 - by Dr Zara Mahmoud 
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14 March 2011 - by MacKenna Roberts 
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Gingrich wants panel to look at IVF clinics

13 February 2012

By Ruth Retassie

Appeared in BioNews 644

US Republican presidential candidate Newt Gingrich has called for a commission to investigate the ethical issues around IVF. He also wants a ban on human embryonic stem cell (ES cell) research, including research on donated embryos left over from IVF.

'I believe life begins at conception, and the question I was raising was what happens to embryos in fertility clinics[...] I would favour a commission to look seriously at the ethics of how we manage fertility clinics', Gingrich told an audience outside a Baptist church in Florida.

Gingrich, a former speaker in the US House of Representatives, is attempting to appeal to the conservative audience by changing his stance on human ES cell research. He has a long history of politically supporting scientific research, including human ES cell research in 2001.

He now questions the ethics behind IVF and the management of embryos in clinics. Gingrich did not expand on his comments, but they indicate support for a greater role of the federal government in regulating IVF. Federal legislation currently only requires fertility clinics to document rates of success.

Referring to human ES cell research as 'the use of science to desensitise society over the killing of babies', Gingrich is taking a strong stance on the issue. 'If you have IVF, you are creating life; therefore, we should look seriously at what the rules should be for clinics that are doing that, because they are creating life', he said.

Stem cell research has been a key political battleground in the USA over the past decade. Former president, George Bush, restricted funding for new human ES cell research in 2001 to the 21 cell lines that were already being used for research. President Barack Obama approved federal funding for new cell lines when he came into office but the decision is currently being challenged in the courts.

 

SOURCES & REFERENCES
NPR | 30 January 2012
 
Gingrich says commission should look at in vitro clinic management of embryos
StarTribune national | 29 January 2012
 
Washington Post | 29 January 2012
 

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19 December 2011 - by Antony Blackburn-Starza 
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A ruling from a US federal appeals court means that blood stem cell donors may now receive a form of payment for their donation. A federal law that prohibits payment for organs does not apply to stem cells taken from bone marrow using a new method which avoids the extraction of bone marrow itself, the court said.... [Read More]
21 November 2011 - by Dr Morven Shearer 
On 8 November the Mississippi electorate voted against an amendment to the Bill of Rights in their state Constitution which would have redefined life as beginning at the moment of fertilisation – the so-called 'personhood amendment' (Proposition 26)... [Read More]
21 November 2011 - by Dr Gabrielle Samuel 
There was a six percent rise last year in the number of fertility treatments carried out in the UK, according to the Human Fertilisation and Embryology Authority (HFEA)... [Read More]



Gay man who donated sperm to lesbian ex-wife seeks parental access

13 February 2012

By Dr Linda Wijlaars

Appeared in BioNews 644

The Court of Appeal in the UK is hearing a case in which a gay man is fighting for greater parental access to his two-year old son he fathered with his lesbian ex-wife.

The mother says she made a pact with the father during a restaurant meeting before the boy was conceived. In the deal she and her partner would fill the role of primary parents and he would not seek to exercise his parental rights.

The court heard that the father and biological mother used to be in a marriage of convenience and are now divorced. The man currently has five hours visiting contact with his son every two weeks. In order for him to have his son stay overnight, and to able to take him on a holiday, the father wants this visiting contact to be gradually extended.

The mother and her partner say they feel 'bitter and betrayed' after the father made his demands. Mr Charles Howard, QC, representing the couple, said they acknowledge that they are an alternative family to an extent but still 'hold very traditional views of family life and would not have chosen to bring a child into anything other than an intact, two-parent, family'.

Howard added that his clients believe it is in their son's best interest to have one home, rather than two.

Mr Alex Verdan, QC, acting for the father, said that the man had 'described vividly to the court the pleasure and joy that he feels in interacting with his son when they see each other'. He added: 'The father wants to play a full part in his development. He has a strong desire to develop a father-son relationship with the boy'.

Under UK law, donors who donate their sperm through a licensed fertility clinic are not considered as legal parents of the children they help conceive. A donor who donates sperm outside the context of a licensed clinic (for example, to a friend or a donor found through a website online) does not acquire this automatic protection and may be treated as the legal father of the child.

In a same-sex relationship the woman who gives birth to the child will have legal parenthood status. Her partner's status will depend on a number of factors such as whether they are in a civil partnership and whether they conceive through a licensed clinic.

There are similarities to a custody case from 2010 (reported in BioNews 584), where a gay man was awarded joint residency for two children conceived through IVF. As in this case, the lesbian couple wanted to fill the role of primary parents to their children. However, the father had had parental responsibility from the outset for both children, which gave him legal ground to seek further access. The lesbian couple appealed this decision.

The three judges have reserved their decision until an unspecified later date.

 

SOURCES & REFERENCES
Gay man fights for paternal access to child he fathered with lesbian
Pink Paper | 07 February 2012
 
Daily Telegraph | 06 February 2012
 
Mail Online | 06 February 2012
 

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TV Review: Katie - The Science of Seeing Again

13 February 2012

By Rosemary Paxman

Appeared in BioNews 644

Katie: The Science of Seeing Again

Channel 4, Tuesday 7 February 2012

Featuring Katie Piper

'Katie: The Science of Seeing Again', Channel 4, Tuesday 7 February 2012 (featuring Katie Piper)


Following a brutal acid attack, Katie Piper has undergone 109 operations to rebuild her face, however it is the 110th that could change her life. By using pioneering stem cell treatment, Katie hopes to restore the sight to her badly damaged left eye.

Fascinated by this cutting-edge regenerative treatment and keen to better understand how the invasive procedure works, Katie embarks on an exploration of stem cell science.

The Channel 4 documentary 'Katie: The Science of Seeing Again' follows her journey as she researches and undergoes optical surgery. And it's not just the science that Katie explores; she also investigates the treatment's long-term impact, ethical implications and side effects, all the while hoping it will bring the breakthrough she dreams of.

'Of all my injuries, it's the damage to my left eye that has the most impact. The hardest part is not being able to see anything on one side. In crowded places, it leaves me feeling scared and vulnerable,' Katie explains. A chance viewing of a TV programme first introduced Katie to eye surgeon Mr Sheraz Daya and his work on stem cell technology.

'I watched him carry out surgery on both eyes of a man. I couldn't help but think "What if he can help me?"' says Katie.

The procedure that Mr Daya has developed involves injecting the eye with a local anaesthetic and placing a sheet of donor stem cells over the eye. These then stimulate the patient's own stem cells to grow and re-build the damaged eye.

Viewers expecting a detailed account of the science behind this stem cell treatment could find the documentary leaving a few unanswered questions, as the programmes focuses more on Katie's journey, rather than the specifics of the procedure.

In order to gain a better idea of what she may be letting herself in for, Katie visits a woman who has already undergone stem cell treatment to help restore her vision. Her treatment was successful, but there is a downside; Katie learns that a lifetime of anti-rejection drugs awaits her.

Katie then wonders if other options are available and if there mightn't be a way to use her own stem cells for a cornea transplant, rather than being dependent on donors.

This question ultimately leads her to the lab of Dr Doris Taylor of the University of Minnesota, whose team has been able to grow a rat heart from its own embryonic stem cells, removing the risk of rejection.

But this is early stage research and Dr Taylor's work has a way to go before entering the clinic. Nevertheless this leads Katie into the ethical debate surrounding human embryonic stem cell (hESC) research, which involves the use or destruction of human embryos.

Throughout the programme, I was struck by Katie's calm in the face of the many issues that surround stem cell research and which may impact on her own choice of treatment. At one point Dr Freda Bush, a gynaecologist and anti-hESC activist from Mississippi, asks Katie, 'What makes your life more important than that of an embryo?'

Even though Katie's treatment does not use hESCs it would have been understandable if she just landed unthinkingly on the side of hESC research. But, no, she listened to Dr. Bush's views considerately and responded calmly and coherently despite the difference of opinion.

As her operation approaches, Katie begins to wonder if she her expectations are realistic. It was hard not to feel for Katie by this point and I found myself willing everything to go well..

The operation itself was fascinating viewing, a showcase for the intricate work of Mr Daya and his team as they put the new cornea, grown from donor stem cells, in place. The following days proved a real test for Katie's positivity and three weeks after the procedure there was little improvement in her vision. Katie starts to come to terms with the idea that the treatment might not bring the success she'd hoped for.

But one month later there's a breakthrough. 'The appearance of the eye has changed. The redness has gone and my pupil is back. Before, if I tried to put my mobile phone down on the table I'd just drop it on the floor. Now, for the first time since the attack, I'm getting it right', she explains.

'Katie: The Science of Seeing Again' explains the extraordinary journey Katie made to regain vision in her left eye after a brutal acid attack over three years ago. It's a well-rounded programme, concentrating not only on the life-changing medical potential of stem cell science, but some of the ethical implications of hESC research, the long term treatment effects and chances of success, showing stem cell therapies in a realistic light - no mean feat for prime time TV!

 

SOURCES & REFERENCES
Channel 4 | 07 February 2012
 

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